The aim of this proposal is to determine whether the treatment of co-occurring psychiatric disorder(s) will improve the outcomes of substance use (e.g., frequency of drug use, quality of life) when combined with substance-related treatment that is normally provided to adolescents in community addiction treatment settings. In addition, this study will determine whether the systematic treatment of attention-deficit hyperactivity disorder (ADHD) and/or major depressive disorder (MDD) will result in greater symptomatic improvement of the targeted disorder(s) compared with treatment as usual (TAU). ADHD and MDD will be targeted because these two conditions frequently co-occur with substance use disorders (SUD) in adolescents, and evidence-based, efficacious pharmacological treatments for each disorder are available for clinical use.Adolescents with SUD who also have ADHD and/or MDD will be randomized to receive either TAU or TAU in conjunction with systematic treatment for ADHD and/or MDD. The treatment of ADHD and/or MDD will be based on medication algorithms that facilitate a systematic approach for therapeutic decision-making, and thereby decrease the variance in treatment approaches and enhance patient outcomes. The algorithms are based on integrated knowledge of research information and clinical experience. Thus, they can be used both in research and clinical practice. They are user-friendly and offer step-by-step medication decision trees as well as procedural details for implementation.